RESUMEN
BACKGROUND: Patients with diabetes mellitus (DM) remain at high risk for stent restenosis and adverse cardiovascular events in the drug-eluting stent era. The amphilimus-eluting stent (AES) is a third generation reservoir-based polymer-free drug-eluting stent that has shown promising preliminary results in patients with DM. It has been suggested that the formulation of the drug with fatty acids could not only modulate the drug release in a timely manner but also achieve convenient levels of drug concentration in diabetic cardiac cells. The aim of this trial is to assess the efficacy of the AES in patients with DM compared with the cobalt chromium everolimus-eluting stent with non-erodible polymer (EES). STUDY DESIGN: This is an investigator-initiated, multicenter, randomized clinical trial, performed in patients with DM. A total of 112 diabetic patients receiving glucose-lowering agents and requiring percutaneous revascularization of a de novo lesion will be randomized in a 1:1 fashion to receive AES or EES. The primary endpoint is the neointimal volume obstruction at 9 months, evaluated by optical coherence tomography. Secondary endpoints will include strut coverage, angiographic in-stent late loss and clinical endpoints such as target vessel revascularization or probable/definite stent thrombosis. This study completed the inclusion in October 2013. CONCLUSIONS: The RESERVOIR trial is an investigator-initiated trial that will evaluate whether the polymer-free AES is not inferior to the EES inhibiting the neointimal hyperplasia in patients with DM. These results are also expected to improve our knowledge of the neointimal healing process in this population (Clinicaltrials.gov number NCT01710748).
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Fármacos Cardiovasculares/administración & dosificación , Enfermedad de la Arteria Coronaria/terapia , Angiopatías Diabéticas/terapia , Stents Liberadores de Fármacos , Everolimus/administración & dosificación , Ácidos Grasos/administración & dosificación , Intervención Coronaria Percutánea/instrumentación , Polímeros/química , Proyectos de Investigación , Aleaciones de Cromo , Protocolos Clínicos , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico , Reestenosis Coronaria/etiología , Trombosis Coronaria/etiología , Angiopatías Diabéticas/diagnóstico , Humanos , Neointima , Intervención Coronaria Percutánea/efectos adversos , Diseño de Prótesis , España , Factores de Tiempo , Tomografía de Coherencia Óptica , Resultado del TratamientoAsunto(s)
Plaquetas/efectos de los fármacos , Servicios Médicos de Urgencia , Infarto del Miocardio/terapia , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/administración & dosificación , Agregación Plaquetaria/efectos de los fármacos , Ticlopidina/análogos & derivados , Anciano , Bélgica , Plaquetas/metabolismo , Clopidogrel , Trombosis Coronaria/etiología , Esquema de Medicación , Femenino , Humanos , Ataque Isquémico Transitorio/etiología , Italia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/mortalidad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/mortalidad , Pruebas de Función Plaquetaria , Recurrencia , Stents , Accidente Cerebrovascular/etiología , Ticlopidina/administración & dosificación , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Angioplastia Coronaria con Balón , Arildialquilfosfatasa/genética , Plaquetas/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Polimorfismo Genético , Ticlopidina/análogos & derivados , Anciano , Clopidogrel , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ticlopidina/farmacologíaRESUMEN
Thienopyridines are a class of drug targeting the platelet adenosine diphosphate (ADP) 2 receptor. They significantly reduce platelet activity and are therefore clinically beneficial in settings where platelet activation is a key pathophysiological feature, particularly myocardial infarction. Ticlopidine, the first of the class introduced to clinical practice, was soon challenged and almost completely replaced by clopidogrel for its better tolerability. More recently, prasugrel and ticagrelor have been shown to provide a more powerful antiplatelet action compared to clopidogrel but at a cost of higher risk of bleeding complications. Cangrelor, a molecule very similar to ticagrelor, is currently being evaluated against clopidogrel. Considering the key balance of ischemic protection and bleeding risk, this paper discusses the background to the development of prasugrel, ticagrelor, and cangrelor and aims to characterise their risk-benefit profile and possible implementation in daily practice.
RESUMEN
BACKGROUND: On top of aspirin, an abciximab bolus-only regimen results in a 30% drop in platelet inhibition at 6 h as compared with the on-label regimen. The concomitant administration of high loading dose clopidogrel, by bridging with abciximab bolus, may sustain suppression of platelet activity over time. OBJECTIVES: To investigate the non-inferiority of abciximab bolus-only and concomitant high loading dose clopidogrel vs. abciximab bolus + infusion with respect to the inhibition of platelet aggregation (IPA) as determined by light transmission aggregometry. PATIENTS/METHODS: Seventy-three patients with non-ST segment elevation acute coronary syndromes underwent double-blind randomization to abciximab bolus followed by a 12-h placebo infusion and concomitant 600-mg clopidogrel vs. abciximab bolus + a 12-h infusion and 300 mg of clopidogrel. IPA was determined by light transmission aggregometry throughout 24 h. Clopidogrel poor responsiveness was defined as ≥ 50% 5 µmol L⻹ ADP-induced maximum platelet aggregation. RESULTS: In clopidogrel responders (n = 68), IPA after 20 µmol L⻹ ADP at 4 h was 89% ± 13% in the bolus-only arm vs. 92% ± 14% in the bolus + infusion arm (P = 0.011 for non-inferiority). IPA after 5 or 20 µmol L⻹ ADP and 5 or 15 µmol L⻹ TRAP and the proportion of patients showing ≥ 80% IPA did not differ at any time point, irrespective of clopidogrel responsiveness status. Thirty-day outcomes were similar, whereas hemoglobin (0.91 ± 0.8 vs. 0.5 ± 0.7 g dL⻹ ; P = 0.01) and platelet count mean drop (41.7 ± 57 vs. 18.6 ± 34 109 L⻹; P = 0.042) were significantly reduced in the bolus-only arm. CONCLUSIONS: Withholding abciximab post-bolus infusion in patients receiving high loading dose clopidogrel does not impair platelet inhibition throughout 24 h, and has the potential to improve the safety profile of the drug at reduced costs.
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Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Plaquetas/efectos de los fármacos , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Agregación Plaquetaria/efectos de los fármacos , Ticlopidina/análogos & derivados , Abciximab , Anciano , Angiografía/métodos , Clopidogrel , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pruebas de Función Plaquetaria , Stents , Ticlopidina/administración & dosificación , Ticlopidina/uso terapéutico , Factores de TiempoRESUMEN
Thienopyridines are a class of drug targeting the platelet adenosine diphosphate 2 receptor. They have been shown to significantly reduce platelet activity exerting an important role in those clinical settings in which such an effect is beneficial. Ticlopidine was first to be introduced several years ago but it was quickly replaced by clopidogrel as it had a better risk/benefit profile. Recently, prasugrel has been developed and tested in several ex vivo studies and clinical trials showing able to provide a more powerful antiplatelet effect at the expense of a higher risk of bleeding complications. Great debate rose around its recent approval in the US as well as in Europe. This review aims at exploring the development and available clinical data of this third-generation thienopyridine while discussing its practical implementation in routine practice.
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Piperazinas/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Receptores Purinérgicos P2/uso terapéutico , Tiofenos/uso terapéutico , Ticlopidina/análogos & derivados , Clopidogrel , Evaluación Preclínica de Medicamentos , Hemorragia/complicaciones , Humanos , Piperazinas/antagonistas & inhibidores , Piperazinas/farmacocinética , Inhibidores de Agregación Plaquetaria/farmacocinética , Clorhidrato de Prasugrel , Antagonistas del Receptor Purinérgico P2 , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Tiofenos/antagonistas & inhibidores , Tiofenos/farmacocinética , Ticlopidina/farmacocinética , Ticlopidina/uso terapéuticoRESUMEN
AIM: To compare the long-term relative efficacy and safety of SES and PES in patients undergoing percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) disease and to evaluate the role of lesion location and stenting technique in determining outcomes. METHODS AND RESULTS: From April 2002 to April 2004, 288 consecutive patients who underwent elective PCI with DES implantation for de novo lesions on ULMCA have been retrospectively selected and analyzed in seven European and US tertiary care centers. All patients had a minimum follow-up of 3 years. SES was used in 152 patients while 136 received PES. Isolated ostial-shaft disease was present in 27% of patients. Distal LM disease (73%) was treated with single and double stent approach in 29.5% and 43.4% of patients respectively. After 3 years, rates of survival free from any of the events investigated, were independent from lesion location and stenting approach and did not differ significantly between SES and PES groups. Freedom from MACE (SES vs. PES) was 76.3% vs. 83.1% in the ostial/shaft group, 80.3% vs. 72.8% in the distal-single stent group and 67.1% vs. 66.2% in the distal-double stent group. Definite stent thrombosis occurred only in 1(0.3%) patient at 439 days. CONCLUSIONS: In elective patients who underwent PCI for de novo lesions in the ostium, shaft or distal ULMCA, long-term clinical outcomes with SES and PES use were similar independently of lesion location and stenting technique.
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Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Vasos Coronarios/patología , Stents Liberadores de Fármacos , Paclitaxel/administración & dosificación , Sistema de Registros , Sirolimus/administración & dosificación , Anciano , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/efectos de los fármacos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: Hypertrophic obstructive cardiomyopathy (HOCM) often leads to heart failure, severe symptoms and death. Percutaneous transluminal septal myocardial ablation (PTSMA) by alcohol injection efficiently reduces left ventricular (LV) outflow tract pressure gradient and improves symptoms. We determined acute changes in haemodynamics and systolic and diastolic LV function after PTSMA. METHODS: In 17 consecutive patients with symptomatic HOCM referred for PTSMA, the target vessel was determined by myocardial contrast transthoracic echocardiography. An over-the-wire balloon was inflated in the target vessel and multiple 0.5-ml alcohol injections were performed. LV systolic and diastolic function was assessed by online pressure-volume loops obtained by conductance catheter at baseline and acutely after the procedure. RESULTS: In all patients except two, a single septal branch was treated using a total of 2.0 (0.5) ml ethanol per patient. The rest and post-extrasystolic gradient were significantly decreased after PTSMA (79 (38) to 14 (16) mm Hg and 130 (50) to 34 (33) mm Hg, respectively, both p<0.001). Ejection fraction decreased (78% (9%) to 67% (13%), p<0.001). Cardiac output, heart rate and stroke work were unchanged, but systolic and diastolic volume increased. End-systolic and end-diastolic pressure significantly decreased (166 (27) to 129 (26) mm Hg, p<0.001 and 25 (6) to 21 (7) mm Hg, p = 0.049, respectively). Significant rightward shift (p<0.001) and decreased slope (p = 0.041) of the end-systolic pressure-volume relation indicated reduced contractility, whereas diastolic stiffness, -dP/dt(MIN), and tau were significantly improved after the procedure. CONCLUSIONS: PTSMA acutely reduced systolic function but promptly improved diastolic function with maintained cardiac output and stroke work. Improved diastolic function and increased end-diastolic volume compensated for the systolic loss and resulted in maintained haemodynamics.
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Cardiomiopatía Hipertrófica/tratamiento farmacológico , Etanol/administración & dosificación , Solventes/administración & dosificación , Cardiomiopatía Hipertrófica/fisiopatología , Cateterismo , Femenino , Hemodinámica , Humanos , Inyecciones Intralesiones , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
BACKGROUND: Because of the recently published results of the MAGIC study there is confusion as to whether administration of granulocyte-colony stimulating factor (G-CSF) after acute myocardial infarction (MI) should be regarded as a potentially harmful treatment. This meta-analysis of appropriate clinical studies is intended to show the impact of G-CSF given after MI on aggravated incidence of coronary re-stenosis or progression of coronary lesions. METHODS: We used a fixed effects model based on the Mantel-Haenszel method to combine results from the different trials. These studies provided the basis for the current analysis comprising 106 patients of whom 62 were subjected to G-CSF treatment. RESULTS: Minimum lumen diameter (MLD) measured immediately after percutaneous coronary intervention (PCI) was similar in both groups with a diameter stenosis of 12.3% (SD 9.5%) in the G-CSF group and 10.3% (8.5%) in the control group (p = 0.32). At follow-up, both MLD and percentage stenosis were not different between G-CSF-treated and control patients. Subsequently, averaged late lumen loss revealed similar results and no differences between groups (p = 0.11), and neither stent thrombosis nor re-infarction in either group. CONCLUSIONS: The current meta-analysis of clinical reports fails to justify an elevated risk for coronary re-stenosis after PCI in acute MI or adverse events following G-CSF in the setting of MI when used after state of the art treatment in carefully conducted clinical protocols.
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Angioplastia Coronaria con Balón/métodos , Cardiomegalia/etiología , Reestenosis Coronaria/etiología , Vasos Coronarios/patología , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Infarto del Miocardio/tratamiento farmacológico , Angioplastia Coronaria con Balón/efectos adversos , Cardiomegalia/patología , Angiografía Coronaria/métodos , Vasos Coronarios/efectos de los fármacos , Interpretación Estadística de Datos , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Masculino , Infarto del Miocardio/patología , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess the potential relation between plaque composition and vascular remodelling by using spectral analysis of intravascular ultrasound (IVUS) radiofrequency data. METHODS AND RESULTS: 41 coronary vessels with non-significant (< 50% diameter stenosis by angiography), < or = 20 mm, non-ostial lesions located in non-culprit vessels underwent IVUS interrogation. IVUS radiofrequency data obtained with a 30 MHz catheter, were analysed with IVUS virtual histology software. A remodelling index (RI) was calculated and divided into three groups. Lesions with RI > or = 1.05 were considered to have positive remodelling and lesions with RI < or = 0.95 were considered to have negative remodelling. Lesions with RI > or = 1.05 had a significantly larger lipid core than lesions with RI 0.96-1.04 and RI < or = 0.95 (22.1 (6.3) v 15.1 (7.6) v 6.6 (6.9), p < 0.0001). A positive correlation between lipid core and RI (r = 0.83, p < 0.0001) and an inverse correlation between fibrous tissue and RI (r = -0.45, p = 0.003) were also significant. All of the positively remodelled lesions were thin cap fibroatheroma or fibroatheromatous lesions, whereas negatively remodelled lesions had a more stable phenotype, with 64% having pathological intimal thickening, 29% being fibrocalcific lesions, and only 7% fibroatheromatous lesions (p < 0.0001). CONCLUSIONS: In this study, in vivo plaque composition and morphology assessed by spectral analysis of IVUS radiofrequency data were related to coronary artery remodelling.
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Estenosis Coronaria/patología , Vasos Coronarios/patología , Estenosis Coronaria/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , UltrasonografíaRESUMEN
Grey scale intravascular ultrasound (IVUS) is a valuable clinical tool to assess the extent and severity of coronary atheroma. However, it cannot reliably identify plaques with a high-risk of future clinical events. Serial IVUS studies to assess the progression and/or regression of atherosclerotic plaques demonstrated only modest effects, of pharmacological intervention on plaque burden, even when clinical efficacy is documented. Spectral analysis of radiofrequency ultrasound data (IVUS-virtual histology (IVUS-VH), Volcano Therapeutics, Rancho Cordova, CA) has the potential to characterize accurately plaque composition. The Integrated Biomarker and Imaging Study (IBIS) evaluated both invasive and non-invasive imaging techniques along with the assessment of novel biomarkers to characterize sub-clinical atherosclerosis. IVUS-VH was not included at the start of the IBIS protocol. The purpose of this paper is to describe the methodology we used to obtain and analyse IVUS-VH images and the approach to cross-correlations with the other techniques.
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Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador , Ultrasonografía Intervencional/métodos , Biomarcadores/análisis , Cateterismo Cardíaco , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/fisiopatología , Femenino , Humanos , Masculino , Proyectos Piloto , Estudios Prospectivos , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Ultrasonografía Doppler en ColorRESUMEN
OBJECTIVE: To compare clinical outcome of paclitaxel eluting stents (PES) versus sirolimus eluting stents (SES) for the treatment of acute ST elevation myocardial infarction. DESIGN AND PATIENTS: The first 136 consecutive patients treated exclusively with PES in the setting of primary percutaneous coronary intervention for acute myocardial infarction in this single centre registry were prospectively clinically assessed at 30 days and one year. They were compared with 186 consecutive patients treated exclusively with SES in the preceding period. SETTING: Academic tertiary referral centre. RESULTS: At 30 days, the rate of all cause mortality and reinfarction was similar between groups (6.5% v 6.6% for SES and PES, respectively, p = 1.0). A significant difference in target vessel revascularisation (TVR) was seen in favour of SES (1.1% v 5.1% for PES, p = 0.04). This was driven by stent thrombosis (n = 4), especially in the bifurcation stenting (n = 2). At one year, no significant differences were seen between groups, with no late thrombosis and 1.5% in-stent restenosis (needing TVR) in PES versus no reinterventions in SES (p = 0.2). One year survival free of major adverse cardiac events (MACE) was 90.2% for SES and 85% for PES (p = 0.16). CONCLUSIONS: No significant differences were seen in MACE-free survival at one year between SES and PES for the treatment of acute myocardial infarction with very low rates of reintervention for restenosis. Bifurcation stenting in acute myocardial infarction should, if possible, be avoided because of the increased risk of stent thrombosis.
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Angioplastia Coronaria con Balón/métodos , Fármacos Cardiovasculares/uso terapéutico , Infarto del Miocardio/terapia , Paclitaxel/uso terapéutico , Sirolimus/uso terapéutico , Stents , Adulto , Anciano , Materiales Biocompatibles Revestidos , Reestenosis Coronaria/prevención & control , Sistemas de Liberación de Medicamentos , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVES: High concentrations of serum xanthine oxidase (XO) have been reported during human liver disease and hepatocyte injury in experimental settings. However, it is unclear whether this elevation reflects hepatocyte necrosis or has a different meaning. METHODS: The serum level of XO in 64 patients with chronic liver disease (17 patients with cirrhosis, 30 with chronic hepatitis, and 17 with cholestatic disorders) and in 12 control subjects was determined by a competitive ELISA. Conventional serum markers of liver damage were assessed in all patients, and grading and staging were scored in the chronic hepatitis group according to Knodell. RESULTS: The XO serum levels were significantly higher in the patients than in the controls. The differences were also significant when controls were compared to patients with chronic hepatitis and cholestatic disorders separately, but not when compared to the cirrhosis group. Patients with cholestatic disorders had XO values higher than those of patients with cirrhosis or chronic hepatitis. XO levels did not correlate with stage and grade in chronic hepatitis group. We found a weak but significant positive correlation in patients between XO serum level and gamma-glutamyl transpeptidase (r = 0.37). This correlation was stronger when chronic hepatitis (r = 0.42) and, especially cholestatic disorders (r = 0.71), were separately tested, but was absent in the cirrhosis group. The XO values positively correlated with alkaline phosphatase in patients with cholestatic disorders. A level of serum XO >32 microg/ml specifically identified cholestatic disorders in our study population. CONCLUSIONS: A marked elevation of serum XO in patients with chronic liver disease seems to reflect the presence of cholestasis. No correlation between XO levels and histological or serum evidence of hepatocyte necrosis was found in these patients.
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Colestasis/enzimología , Hepatitis Viral Humana/enzimología , Cirrosis Hepática/enzimología , Xantina Oxidasa/sangre , Adulto , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A 65-year-old man was submitted to coronary angioplasty and stent implantation for stable angina. The treatment included a 30-day therapy with ticlopidine (in addition to aspirin, metoprolol, ramipril, amlodipine and nitrates). One month after ticlopidine withdrawal a progressive cholestatic jaundice took place. Viral, immunogenic as well as nutritional causes were ruled out. The abdominal echography disclosed a normal biliary tree and the liver biopsy showed a centrolobular cholestasis pattern. Drug-induced cholestatic reaction was diagnosed and attributed to ticlopidine. There was a progressive improvement in clinical and laboratory findings 4 months after steroid treatment. The clinical picture was normalized after 6 months. When considering the option ticlopidine, even for a short time after coronary angioplasty, the possibility of drug-induced hepatotoxicity should be kept in mind. Consequently, markers of liver toxicity should be monitored carefully.
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Ictericia/inducido químicamente , Inhibidores de Agregación Plaquetaria/efectos adversos , Stents , Ticlopidina/efectos adversos , Anciano , Angioplastia Coronaria con Balón , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Estenosis Coronaria/terapia , Humanos , Masculino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticlopidina/uso terapéutico , Factores de TiempoAsunto(s)
Apoptosis/fisiología , Citocinas/fisiología , Insuficiencia Cardíaca/fisiopatología , Neurotransmisores/fisiología , Acetilcolinesterasa/metabolismo , Angiotensinas/metabolismo , Endotelinas/metabolismo , Corazón/fisiología , Corazón/fisiopatología , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/metabolismo , Humanos , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/fisiopatología , Infarto del Miocardio/etiología , Infarto del Miocardio/fisiopatología , Miocardio/patología , Sistema Nervioso Simpático/fisiopatología , Remodelación Ventricular/fisiologíaRESUMEN
BACKGROUND: Patients with alcoholic cirrhosis have left ventricular dimensions similar to controls. Few data have been reported in patients with cirrhosis of viral origin. AIM: To assess left ventricular dimensions in patients with pure viral cirrhosis. PATIENTS AND METHODS: Thirty patients with virus-related cirrhosis, 23 patients with alcoholic cirrhosis and 12 healthy controls were submitted to measurement of left ventricular volumes, cardiac output, mean arterial pressure and total peripheral resistance. RESULTS: Patients with cirrhosis showed a similar increase in cardiac index and heart rate and reduction of mean arterial pressure and peripheral vascular resistance in comparison to controls, irrespective of the aetiology. Left ventricular end systolic volume index was lower (p<0.01) and ejection fraction higher (p<0.01) in virus-related cirrhotic patients [mean +/- SD, respectively 12.4+/-4.1 ml/sqm and 77.9%) in comparison both to controls (21.5+/-6.3 ml/sqm and 66.8%) and alcoholics (20.6+/-7.0 ml/sqm and 68.8%). End diastolic volume index was not significantly different between the three groups. CONCLUSIONS: Our findings indicate smaller left ventricular volumes and higher ejection fraction in pure virus-related cirrhosis than in alcoholic cirrhosis and controls. Since peripheral haemodynamics proved similar in virus- and alcohol-related cirrhosis, a subclinical alcohol cardiomyopathy may be hypothesised to account for the absence of such left ventricular pattern in alcoholic patients.
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Ventrículos Cardíacos/patología , Cirrosis Hepática/patología , Presión Sanguínea , Gasto Cardíaco , Femenino , Frecuencia Cardíaca , Hepatitis Viral Humana/complicaciones , Humanos , Cirrosis Hepática/fisiopatología , Cirrosis Hepática Alcohólica/patología , Cirrosis Hepática Alcohólica/fisiopatología , Masculino , Persona de Mediana Edad , Volumen Sistólico , Resistencia VascularRESUMEN
A method for the measurement of reactive oxygen species (ROS) in human hepatic tissue has been developed. The method is based on the EPR detection of the nitroxide radical produced by reaction of the hydroxylamine spin-probe bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate with ROS generated under pseudo-physiologic conditions in fine needle biopsies of healthy (10 controls) and diseased (22 patients) human liver. Measures of malonaldehyde in 9 liver biopsies (3 controls and 6 patients) have also been obtained by high pressure liquid chromatography and values parallel those obtained by the spin-probe technique. The amount of ROS found in healthy human liver (median = 1.8 x 10(-11) mol/mg) was significantly lower than values found in liver affected by hepatitis B (median=5.8 x 10(-10) mol/mg; p < 0.02) or by hepatitis C (median = 2.7 x 10(-9) mol/mg; p < 0.003) as well as compared to some other non-viral liver diseases (NVLD): autoimmune hepatitis, primary biliary cirrhosis, primary schlerosing cholangitis (median = 9.8 x 10(-9) mol/mg; p < 0.005). NVLD also showed significantly higher ROS levels compared to hepatitis B (p < 0.04) and hepatitis C (p < 0.04). The mechanism, potentiality and limitations of our method are discussed.